Temozolomide and Radiation Therapy in Treating Patients With Gliomas

OBJECTIVES:

- Compare the 3-year survival of patients with high-risk low-grade gliomas treated with
temozolomide and radiotherapy followed by temozolomide alone with that of patients
enrolled on European Organization for Research and Treatment of Cancer (EORTC)clinical
trials EORTC-22844 and EORTC-22845.

- Determine the toxicity of this regimen in these patients.

- Determine the association between progression-free survival and O6-methylguanine-DNA
methyltransferase (MGMT) methylation status in patients treated with this regimen.

- Determine the association between survival and MGMT methylation status in patients
treated with this regimen.

- Determine the quality of life (QOL) of patients treated with this regimen.

- Determine the neurocognitive function of patients treated with this regimen.

- Evaluate the feasibility of collecting patient-reported QOL and neurocognitive
assessments over 3 years.

OUTLINE: This is a non-randomized, multicenter study.

Patients receive oral temozolomide once daily on days 1-42 and undergo radiotherapy once
daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40, one hour before RT weekdays, in the
evening weekends. Beginning 28 days after completion of chemoradiotherapy, patients receive
oral temozolomide once daily on days 1-5. Treatment with temozolomide repeats every 28 days
for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, 6 months, 12 months.

After completion of study treatment, patients are followed at 4 months, every 6 months for 2
years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 135 patients will be accrued for this study within 44 months.

DISEASE CHARACTERISTICS:

- Histologically confirmed* supratentorial glioma of 1 of the following histologies:

- Astrocytoma (diffuse fibrillary, protoplasmic, or gemistocytic)

- Oligodendroglioma

- Oligoastrocytoma Note: *Histologic atypia allowed provided no other histologic
features (i.e., frequent mitoses, endothelial proliferation, and/or acute
necrosis) that would result in a designation of anaplastic astrocytoma,
anaplastic mixed oligodendroglioma or oligoastrocytoma, or glioblastoma
multiforme are present

- Unifocal or multifocal disease

- World Health Organization (WHO) grade II disease

- Neurofibromatosis allowed

- Surgical biopsy or resection for tumor tissue sampling required within the past 12
weeks

- Tissue block or core biopsy available for O6-methylguanine-DNA methyltransferase
analysis and tissue banking

- Patients who have only had a stereotactic biopsy are not eligible

- Must have ≥ 3 of the following risk factors:

- Age 40 and over

- Largest preoperative tumor diameter ≥ 6 cm

- Tumor crosses the midline

- Astrocytoma-dominant tumor subtype

- Preoperative Neurological Function Status > 1

- No other low-grade glioma histologies, including any of the following:

- Pilocytic astrocytoma

- Subependymal giant cell astrocytoma of tuberous sclerosis

- Subependymoma

- Pleomorphic xanthoastrocytoma

- Presence of a neuronal element, such as ganglioglioma

- Dysneuroembryoplastic epithelial tumor

- No high-grade glioma, including any of the following:

- Anaplastic astrocytoma

- Glioblastoma multiforme

- Anaplastic oligodendroglioma

- Anaplastic oligoastrocytoma

- No tumors in any non-supratentorial location, including any of the following:

- Optic chiasm

- Optic nerve(s)

- Pons

- Medulla

- Cerebellum

- Spinal cord

- No evidence of disease progression to spinal meninges or noncontiguous cranial
meninges (i.e., leptomeningeal gliomatosis) by MRI of the spine or cerebrospinal fluid
(CSF) cytology

- MRI of the spine or CSF cytology are not required for patients without symptoms
of spinal/cranial meningeal disease progression

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Zubrod 0-2

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

Hepatic

- Total bilirubin ≤ 1.5 mg/dL

- Serum glutamate oxaloacetate transaminase (SGOT) or Serum glutamate pyruvate
transaminase (SGPT) ≤ 2 times normal

- Alkaline phosphatase ≤ 2 times normal

Renal

- Serum creatinine ≤ 1.5 mg/dL

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No known HIV positivity

- No other malignancy within the past 5 years except carcinoma in situ of the cervix or
nonmelanoma skin cancer

- No active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No concurrent immunotherapy or biologic therapy

Chemotherapy

- No prior chemotherapy

- No other concurrent chemotherapy

Endocrine therapy

- Not specified

Radiotherapy

- No prior radiotherapy to the head and neck unless head and neck radiotherapy clearly
excluded the brain (e.g., localized radiotherapy to the vocal cords)

- No prior radiotherapy to the brain

- No concurrent intensity modulated radiotherapy

- No concurrent stereotactic boost radiotherapy

Surgery

- See Disease Characteristics

Other

- No other concurrent investigational agents